Page 74 - 2014 Printable Abstract Book
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scenarios will involve low-dose rate (LDR) exposures such as by internal emitters as well as external
radiation sources. A critical issue is whether reliable signals can be obtained from biofluids, such as urine
90
or serum, after LDR irradiation. Internal exposure to 137 Cs or Sr as well as LDR external beam
[[Unsupported Character - Symbol Font γ]] rays produced robust and persistent responses with substantial
overlap, yet with notable differences with respect to HDR [[Unsupported Character - Symbol Font γ]] rays;
an overview of these radiation responses will be discussed. Another challenge for radiation metabolomics
is development of informatics approaches for noisy datasets, such as may occur in an actual emergency
where the sheer variability of experimentally irrelevant factors that cannot be controlled for. To address
this issue, Selective Paired Ion Contrast (SPICA) has been developed with the intent of extracting
biologically relevant information from the noisiest of metabolomic data sets. SPICA relies on analyzing all
possible ion-pair combinations in a metabolomic data set, rather than single ions, circumventing situations
where no single metabolite can be used for normalization. Statistical comparisons between sample groups
are made only by analyzing the differences in these pairs. SPICA was able to identify perturbed metabolic
pathways and outperform single-ion based binary classifiers during analysis of two clinical human urine
data sets. With modern instrumentation and customized informatics approaches, radiation metabolomics
is well-positioned to facilitate radiobiology research at both the basic and applied levels.
S19 PARTICLE RADIATION EFFECTS ON CNS
The space environment is comprised of a wide spectrum of highly energetic and charge particle radiation.
Exposure to this type of galactocosmic radiation (GCR) or unplanned solar particle events (SPE) may pose
a potential health hazard to human in planned long-term manned space explorations. Depending on the
radiation dose and beam quality, particle radiation may cause significant damage and oxidative stress in
cells in the Central Nervous System, leading to dysfunction in cellular processes that are associated with
signaling pathways in many different cell types within the CNS, precipitating potential short term cognitive
dysfunction, long term neuropathology or accelerating neurodegeneration. Research in space-relevant
low doses of particle radiation to establish the mechanistic basis for observed CNS endpoints leading to
early or late cognitive and behavioral changes are important to understand how radiation quality, dose
and dose rates impact CNS endpoints. The presentations included in this symposium address state-of-the
art research in the area of particle radiation effects on the CNS. The areas covered include innovative
proteomic profiling approaches to guide the interrogation of neuroproteome after a low dose of particle
radiation; identification of specific markers in the neuroinflammatory signaling pathways that links
radiation induced cognitive impairment to innate immune responses; the use of neurodegenerative
disease animal models to ask the question of whether high LET radiation increases the risk of common
neurodegenerative disease development; and whether high LET radiation impacts the functional integrity
and neuronal network stability through epigenetic mechanisms.
(S1901) Interrogating the neuroproteome for clues to the mechanism of HZE-induced neurocognitive
impairment. Richard A. Britten, Eastern Virginia Medical School, Norfolk, VA
INTRODUCTION. Previous ground-based experiments have demonstrated that exposure to low (~20 cGy)
doses of HZE particles, such as 1 GeV/n 56Fe, results in pronounced deficits in several neurocognitive
domains: novel object recognition, spatial memory and attentional set shifting (ATSET). It is thus possible
72 | P a g e
radiation sources. A critical issue is whether reliable signals can be obtained from biofluids, such as urine
90
or serum, after LDR irradiation. Internal exposure to 137 Cs or Sr as well as LDR external beam
[[Unsupported Character - Symbol Font γ]] rays produced robust and persistent responses with substantial
overlap, yet with notable differences with respect to HDR [[Unsupported Character - Symbol Font γ]] rays;
an overview of these radiation responses will be discussed. Another challenge for radiation metabolomics
is development of informatics approaches for noisy datasets, such as may occur in an actual emergency
where the sheer variability of experimentally irrelevant factors that cannot be controlled for. To address
this issue, Selective Paired Ion Contrast (SPICA) has been developed with the intent of extracting
biologically relevant information from the noisiest of metabolomic data sets. SPICA relies on analyzing all
possible ion-pair combinations in a metabolomic data set, rather than single ions, circumventing situations
where no single metabolite can be used for normalization. Statistical comparisons between sample groups
are made only by analyzing the differences in these pairs. SPICA was able to identify perturbed metabolic
pathways and outperform single-ion based binary classifiers during analysis of two clinical human urine
data sets. With modern instrumentation and customized informatics approaches, radiation metabolomics
is well-positioned to facilitate radiobiology research at both the basic and applied levels.
S19 PARTICLE RADIATION EFFECTS ON CNS
The space environment is comprised of a wide spectrum of highly energetic and charge particle radiation.
Exposure to this type of galactocosmic radiation (GCR) or unplanned solar particle events (SPE) may pose
a potential health hazard to human in planned long-term manned space explorations. Depending on the
radiation dose and beam quality, particle radiation may cause significant damage and oxidative stress in
cells in the Central Nervous System, leading to dysfunction in cellular processes that are associated with
signaling pathways in many different cell types within the CNS, precipitating potential short term cognitive
dysfunction, long term neuropathology or accelerating neurodegeneration. Research in space-relevant
low doses of particle radiation to establish the mechanistic basis for observed CNS endpoints leading to
early or late cognitive and behavioral changes are important to understand how radiation quality, dose
and dose rates impact CNS endpoints. The presentations included in this symposium address state-of-the
art research in the area of particle radiation effects on the CNS. The areas covered include innovative
proteomic profiling approaches to guide the interrogation of neuroproteome after a low dose of particle
radiation; identification of specific markers in the neuroinflammatory signaling pathways that links
radiation induced cognitive impairment to innate immune responses; the use of neurodegenerative
disease animal models to ask the question of whether high LET radiation increases the risk of common
neurodegenerative disease development; and whether high LET radiation impacts the functional integrity
and neuronal network stability through epigenetic mechanisms.
(S1901) Interrogating the neuroproteome for clues to the mechanism of HZE-induced neurocognitive
impairment. Richard A. Britten, Eastern Virginia Medical School, Norfolk, VA
INTRODUCTION. Previous ground-based experiments have demonstrated that exposure to low (~20 cGy)
doses of HZE particles, such as 1 GeV/n 56Fe, results in pronounced deficits in several neurocognitive
domains: novel object recognition, spatial memory and attentional set shifting (ATSET). It is thus possible
72 | P a g e
